Pancreatic cancer is the fifth most common cause of cancer mortality in the United States. The vast majority are considered to be ductal in origin, although considerable controversy exists regarding the actual cell of origin for these exocrine carcinomas. The designation of ductal origin for human tumors by pathologists is based on the ductular (or tubular) appearance of the tumor cells at the level of light microscopy. Yet it has been concluded that both ductular and acinar cells in the normal pancreas can form tubular arrangements, and thus on this basis, acinar cells cannot be eliminated as possible cells of origin for adenocarcinoma. Little is known about the patterns of gene expression in these ductal appearing adenocarcinomas, or how the patterns might compare to those of normal duct or acinar cells. The studies described in this proposal represent a first step in elucidating the patterns of gene expression in pancreatic adenocarcinoma. RNA isolated from human pancreatic adenocarcinoma cell lines will be subjected to blot analysis and hybridized to a nucleic acid cDNA probe to determine if mRNA transcripts corresponding to carbonic anhydrase (an RNA specific to duct cells in the pancreas) are expressed in these cell lines, and if the transcription products of this gene fall in the same size classes in the tumor lines as in the normal pancreas. The RNA preparations from the tumor cell lines will also be subjected to blot hybridization with other nucleic acid probes that are either produced by acinar cells (trypsin, ribonuclease, elastase, and amylase) or islet cells (insulin, glucagon, and somatostatin). In situ hybridization will be performed on thin sections of tumors with the gene probe for carbonic anhydrase, and if time permits, islet specific probes and acinar cell specific probes will also be utilized. We have placed three pancreatic adenocarcinoma surgical specimens in tissue culture: MDA Pancl, MDA Panc2, and MDA Panc3. They will be subjected to further characterization.